Identification and Treatment Of Unstable Plaque with OCT

描述（由申请人提供）：该项目是NIH R 01 EB 002638（原NIH R 01 HL 63953）“提高光学相干断层扫描对易损斑块评估的诊断潜力”的竞争性延续。这项工作的长期目标是开发一种新的高分辨率血管内成像方法，以克服目前心脏诊断的局限性，主要是识别可能导致急性冠状动脉综合征（即心肌梗死或不稳定型心绞痛）的冠状动脉斑块。大多数急性冠脉综合征（ACS）是由冠状动脉中的小斑块而不是大斑块破裂引起的。这些易损斑块是最典型的薄帽纤维粥样硬化（TCFA），其含有相对大量的复杂坏死核心，具有高浓度的脂质和出血，以及覆盖的薄胶原耗尽的内膜帽。当这些斑块破裂时，它们将血栓形成物质释放到血液中，形成凝块，并且血管经常闭塞。这些小斑块超出了任何现有成像模式的检测极限。光学相干断层扫描（OCT），一种新的高分辨率成像方法，已被证明是评估不稳定斑块的巨大潜力。部分通过NIH RO 1 HL 55686和R 01 HL 63953/EB 002638生成的初步数据强烈表明OCT用于易损斑块评估的可行性。10 μ m的分辨率允许前所未有的动脉内微观结构的定义。由于OCT现在被引入用于体内人体成像，允许识别一些TCFA，因此出现了一个重要的问题。大多数ACS由TCFA引起，但大多数TCFA不会导致ACS。虽然OCT可以识别内膜帽小于70 μ m的斑块，这是对其他成像方式的实质性进步，但是OCT需要在识别TCFA之外进一步对这些斑块进行风险分层，这是当前的技术水平。如果该领域的进展要在21世纪继续，人们必须关注具有易受血栓形成影响的病变的高危患者以及导致斑块在精确位置和时间破裂的触发机制。该提案的假设是，可以通过开发辅助技术来推进OCT技术，以改善薄帽动脉粥样硬化的风险分层，识别导致急性冠状动脉综合征的动脉粥样硬化。该假设将通过技术进步、体外人冠状动脉评估、体外RBC注射（出血性）动脉粥样硬化兔斑块成像（目前产生斑块的大型动物模型与人TCFA最相似）、兔动脉粥样硬化斑块体内成像和监测治疗剂诱导的体内变化进行检验。此外，我们将同时尝试通过诱导血管生成来进一步改善兔出血斑块模型，血管生成可能最终是许多斑块破裂的触发因素。

DESCRIPTION (provided by applicant): This program is a competing continuation of NIH R01 EB002638 (formerly NIH R01 HL63953) "Improving the Diagnostic Potential of Optical Coherence Tomography for Vulnerable Plaque Assessment". The long- term objective of this work is to develop a new method of high resolution intravascular imaging to overcome current limitations in cardiac diagnostics, principally the identification of coronary plaques likely to lead to acute coronary syndromes (i.e. myocardial infarction or unstable angina). Most acute coronary syndromes (ACS) result from the rupture of small rather than large plaques in the coronary arteries. These vulnerable plaques are most typically thin cap fibroatheromas (TCFA) that contain a relatively large amount of complex necrotic core with a high concentration of lipid and hemorrhage, and an overlying thin collagen-depleted, intimal cap. When these plaques rupture, they release thrombogenic material into the blood, a clot forms, and the vessel frequently occludes. These small plaques are beyond the detection limit of any currently available imaging modalities. Optical coherence tomography (OCT), a new method of high resolution imaging, has demonstrated great potential for the assessment of unstable plaques. Preliminary data, generated in part through NIH RO1 HL55686 and R01 HL63953/ EB002638, has strongly suggested a feasibility of OCT for vulnerable plaque assessment. The 10 urn resolution allowed unprecedented definition of microstructure within arteries. As OCT is now being introduced for in vivo human imaging, allowing the identification of some TCFA, an important concern arises. Most ACS result from TCFA, but most TCFA do not lead to ACS. While OCT can identify plaques with intimal caps less than 70 urn, a substantial advance over other imaging modalities, a need exists for OCT to further risk stratify these plaques beyond the identification of TCFA, which is the current state of the art. If progress inthe field is to continue in the 21 st century, one must focus on high-risk patients with lesions that are vulnerable to thrombosis together with the triggering mechanisms that cause plaques to rupture at a precise location and time. The hypothesis of this proposal is that OCT technology can be advanced through the development of adjuvant technologies to improve risk stratification of thin cap atheromas, identifying those which lead to acute coronary syndromes. The hypothesis will be tested with advancements of the technology, assessment of in vitro human coronary arteries, imaging of in vitro RBC injected (hemorrhagic) atherosclerotic rabbit plaque (the current large animal model producing plaques most closely resembling human TCFA), in vivo imaging of rabbt atherosclerotic plaque, and monitoring in vivo changes induced with therapeutics. In addition, we will in parallel attempt to further improve the rabbit hemorrhagic plaque model by inducing angiogenesis, the factor which may ultimately be the trigger of many plaque ruptures.